Insights regarding skin regeneration in non-amniote vertebrates: Skin regeneration without scar formation and potential step-up to a higher level of regeneration

Abe, Gembu; Hayashi, Toshinori; Yoshida, Kazuhide; Yoshida, Takafumi; Kudoh, Hidehiro; Sakamoto, Joe; Konishi, Ayumi; Kamei, Yasuhiro; Takeuchi, Takashi; Tamura, Koji; Yokoyama, Hitoshi

doi:10.1016/j.semcdb.2019.11.014

Cited by 20 publications

(11 citation statements)

References 117 publications

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“…Comparative analysis of different wound healing mechanisms depending on species, body sites, and developmental stages is thought to provide a breakthrough in regenerative wound therapy [ 4 ]. Studies of amphibians and teleosts, which are model organisms with the ability to fully regenerate the IOS, suggest that mechanical stress due to the contraction of the wound site may inhibit complete wound regeneration in mammals [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. In addition, a comparative analysis of the human wound healing process in adults and foetuses shows that a weak inflammatory response by undifferentiated foetal immune cells plays an important role in complete foetal IOS regeneration [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction

Kimura

Tsuji

2021

IJMS

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In the past decade, a new frontier in scarless wound healing has arisen because of significant advances in the field of wound healing realised by incorporating emerging concepts from mechanobiology and immunology. The complete integumentary organ system (IOS) regeneration and scarless wound healing mechanism, which occurs in specific species, body sites and developmental stages, clearly shows that mechanical stress signals and immune responses play important roles in determining the wound healing mode. Advances in tissue engineering technology have led to the production of novel human skin equivalents and organoids that reproduce cell–cell interactions with tissue-scale tensional homeostasis, and enable us to evaluate skin tissue morphology, functionality, drug response and wound healing. This breakthrough in tissue engineering has the potential to accelerate the understanding of wound healing control mechanisms through complex mechanobiological and immunological interactions. In this review, we present an overview of recent studies of biomechanical and immunological wound healing and tissue remodelling mechanisms through comparisons of species- and developmental stage-dependent wound healing mechanisms. We also discuss the possibility of elucidating the control mechanism of wound healing involving mechanobiological and immunological interaction by using next-generation human skin equivalents.

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Section: Introductionmentioning

confidence: 99%

Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction

Kimura

Tsuji

2021

IJMS

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“…Adult newts can regenerate various complex tissues or body parts, including a part of the limbs, tail and jaws as well as that of the brain, heart and eyes (lens and retina) [ 4 ]. However, surprisingly, except for limb and tail regeneration, there is limited evidence suggesting that they have the ability to perfectly regenerate their full-thickness skin, although it is widely believed to be so, as supported by a short description of the Iberian ribbed newt, Pleurodeles waltl , in a recently published review [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Skin Wound Healing of the Adult Newt, Cynops pyrrhogaster: A Unique Re-Epithelialization and Scarless Model

et al. 2021

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In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration as they transit to their terrestrial life-stages through metamorphosis, hatching or birth. Therefore, animals that serve as a model for postnatal humans must be an exception to this rule, such as the newt. Here, we evaluated the adult newt in detail for the first time. Using a Japanese fire-bellied newt, Cynops pyrrhogaster, we excised the full-thickness skin at various locations on the body, and surveyed their re-epithelialization, granulation or dermal fibrosis, and recovery of texture and appendages as well as color (hue, tone and pattern) for more than two years. We found that the skin of adult newts eventually regenerated exceptionally well through unique processes of re-epithelialization and the absence of fibrotic scar formation, except for the dorsal-lateral to ventral skin whose unique color patterns never recovered. Color pattern is species-specific. Consequently, the adult C. pyrrhogaster provides an ideal model system for studies aimed at perfect skin wound healing and regeneration in postnatal humans.

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“…This has led to the development of cellular and tissue-based therapies (CTPs) for the treatment of chronic wounds and the success of fish skin xenografts has raised interest in identifying mediators of the effect [ 32 , 33 ]. Furthermore, explaining why fish skin neither scars or wrinkles and has greater regenerative capacity than mammalian skin is of great interest [ 34 ] particularly because the main steps of skin regeneration in vivo are shared [ 35 , 36 , 37 , 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Cartilage Acidic Protein a Novel Therapeutic Factor to Improve Skin Damage Repair?

et al. 2021

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Fish skin has been gaining attention due to its efficacy as a human-wound-treatment product and to identify factors promoting its enhanced action. Skin fibroblasts have a central role in maintaining skin integrity and secrete extra cellular matrix (ECM) proteins, growth factors and cytokines to rapidly repair lesions and prevent further damage or infection. The effects on scratch repair of the ubiquitous but poorly characterized ECM protein, cartilage acidic protein 1 (CRTAC1), from piscine and human sources were compared using a zebrafish SJD.1 primary fibroblast cell line. A classic in vitro cell scratch assay, immunofluorescence, biosensor and gene expression analysis were used. Our results demonstrated that the duplicate sea bass Crtac1a and Crtac1b proteins and human CRTAC-1A all promoted SJD.1 primary fibroblast migration in a classic scratch assay and in an electric cell impedance sensing assay. The immunofluorescence analysis revealed that CRTAC1 enhanced cell migration was most likely caused by actin-driven cytoskeletal changes and the cellular transcriptional response was most affected in the early stage (6 h) of scratch repair. In summary, our results suggest that CRTAC1 may be an important factor in fish skin promoting damage repair.

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Insights regarding skin regeneration in non-amniote vertebrates: Skin regeneration without scar formation and potential step-up to a higher level of regeneration

Cited by 20 publications

References 117 publications

Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction

Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction

Skin Wound Healing of the Adult Newt, Cynops pyrrhogaster: A Unique Re-Epithelialization and Scarless Model

Cartilage Acidic Protein a Novel Therapeutic Factor to Improve Skin Damage Repair?

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